Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota, United States of America.
Division of Infectious Diseases, University of Arizona, Tucson, Arizona, United States of America.
PLoS Pathog. 2019 Mar 21;15(3):e1007311. doi: 10.1371/journal.ppat.1007311. eCollection 2019 Mar.
CD8+ T cells play an important role in controlling of HIV and SIV infections. However, these cells are largely excluded from B cell follicles where HIV and SIV producing cells concentrate during chronic infection. It is not known, however, if antigen-specific CD8+ T cells are excluded gradually as pathogenesis progresses from early to chronic phase, or this phenomenon occurs from the beginning infection. In this study we determined that SIV-specific CD8+ T cells were largely excluded from follicles during early infection, we also found that within follicles, they were entirely absent in 60% of the germinal centers (GCs) examined. Furthermore, levels of SIV-specific CD8+ T cells in follicular but not extrafollicular areas significantly correlated inversely with levels of viral RNA+ cells. In addition, subsets of follicular SIV-specific CD8+ T cells were activated and proliferating and expressed the cytolytic protein perforin. These studies suggest that a paucity of SIV-specific CD8+ T cells in follicles and complete absence within GCs during early infection may set the stage for the establishment of persistent chronic infection.
CD8+ T 细胞在控制 HIV 和 SIV 感染方面发挥着重要作用。然而,在慢性感染期间,HIV 和 SIV 产生细胞集中的 B 细胞滤泡中,这些细胞在很大程度上被排除在外。然而,尚不清楚抗原特异性 CD8+ T 细胞是否随着疾病从早期向慢性阶段的进展而逐渐被排除,或者这种现象是否从感染开始就存在。在这项研究中,我们确定 SIV 特异性 CD8+ T 细胞在早期感染时很大程度上被排除在滤泡之外,我们还发现,在 60%的检查生发中心 (GC) 中,它们完全不存在。此外,滤泡内的 SIV 特异性 CD8+ T 细胞水平与病毒 RNA+细胞水平呈显著负相关,但滤泡外区域则不然。此外,滤泡内的 SIV 特异性 CD8+ T 细胞亚群被激活和增殖,并表达细胞毒性蛋白穿孔素。这些研究表明,在早期感染时,滤泡内 SIV 特异性 CD8+ T 细胞数量不足,GC 内完全不存在,可能为持续慢性感染的建立奠定了基础。